Study 329

Study 329
Paroxetine, sold as Paxil and Seroxat
Study type	Eight-week, placebo-controlled, double-blind, randomized clinical trial comparing paroxetine with imipramine in adolescents with major depressive disorder
Dates	1994–1998
Locations	10 centres in the United States, two in Canada
Lead researcher	Martin Keller, then professor of psychiatry, Brown University
Funding	SmithKline Beecham, now GlaxoSmithKline (GSK)
Protocol	, SmithKline Beecham, 20 August 1993, amended 24 March 1994.
Published	July 2001
Disputed article	Martin B. Keller, et al. (July 2001). "Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial", Journal of the American Academy of Child and Adolescent Psychiatry, 40(7), pp. 762–772. PMID 11437014
Call for retraction	May 2003, April 2013
Retracted	No
Legal penalty	GSK fined in 2012 by US Department of Justice
Study reanalysis	Joanna Le Noury, et al. (16 September 2015). "Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence", BMJ, 351, 16 September 2015. PMID 26376805

Study 329 was a clinical trial conducted in North America from 1994 to 1998 to study the efficacy of paroxetine, an SSRI anti-depressant, in treating 12- to 18-year-olds diagnosed with major depressive disorder. Led by Martin Keller, then professor of psychiatry at Brown University, and funded by the British pharmaceutical company SmithKline Beecham—known since 2000 as GlaxoSmithKline (GSK)—the study compared paroxetine with imipramine, a tricyclic antidepressant, and placebo (an inert pill). SmithKline Beecham had released paroxetine in 1991, marketing it as Paxil in North America and Seroxat in the UK. The drug attracted sales of $11.7 billion in the United States alone from 1997 to 2006, including $2.12 billion in 2002, the year before it lost its patent.

Published in July 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), which listed Keller and 21 other researchers as co-authors, study 329 became controversial when it was discovered that the article had been ghostwritten by a PR firm hired by SmithKline Beecham; had made inappropriate claims about the drug's efficacy; and had downplayed safety concerns. The controversy led to several lawsuits and strengthened calls for drug companies to disclose all their clinical research data. New Scientist wrote in 2015: "You may never have heard of it, but Study 329 changed medicine."

SmithKline Beecham acknowledged internally in 1998 that the study had failed to show efficacy for paroxetine in adolescent depression. In addition, more patients in the group taking paroxetine had experienced suicidal thinking and behaviour. Although the JAACAP article included these negative results, it did not account for them in its conclusion; on the contrary, it concluded that paroxetine was "generally well tolerated and effective for major depression in adolescents". The company relied on the JAACAP article to promote paroxetine for off-label use in teenagers.